The present invention relates to a method for treating patients which are prone to contracting gastric ulcers, and more especially to a method for compensating for the propensity of such patients to have deleterious amounts of bile acids present in the stomach as a result of duodenogastric regurgitation.
Because it is thought that gastric ulcer, and by gastric ulcer is meant an ulcer located in the stomach as opposed to other portions of the gastrointestinal tract, is caused primarily by the action of ulcerogenic factors such as hydrochloric acid and pepsin which disturb the mucous membrane forming the inner lining of the stomach, conventional pharmaco-therapeutical efforts aimed at the treatment of gastric ulcers have heretofore concentrated on controlling the action of hydrochloric acid and pepsin. Specifically, hitherto-known methods for treating gastric ulcer have been directed toward the inhibition of gastrointestinal motility and secretion, the blocking of spasm and the neutralization or counteraction of hydrochloric acid in the gastric juice. There exists also one school of thought contending that gastric ulcer is caused by abnormal action of the central nervous system, and accordingly, treatment by means of various sedatives and/or tranquilizers has been proposed; however, there is virtual consensus that hyperacidity and particularly hyperchlorohydria, i.e., hypersecretion of hydrochloric acid in the stomach, plus the presence of gastric pepsin are primarily responsible for the formation of gastric ulcer. Normally, the mucosal tissues of the stomach are protected by a film of mucin, the mucopolysacchride secreted by the gastric mucosa. It is theorized that the above-mentioned agents disturb the mucous membrane of the stomach and thereby give rise to the formation of ulcers. Accordingly, the heretofore proposed methods of treating the condition known as gastric ucler have focused completely upon counterbalancing the effect of excess hydrochloric acid together with other mineral acids and pepsin. Those modes of treatment which have been employed can be classified generally into the following groups: (1) application of antacid agents to neutralize the excess acid, such agents including conventional inorganic basic salts, colloidal neutralizing agents, anion exchange resins, amino acids, carboxymethylcellulose and the like; (2) application of anti-cholinergic agents; (3) the use of absorbents and adsorbents; and (4) introduction of agents to protect the mucous membrane of the stomach.
In accordance with the present invention, on the other hand, an entirely new method is provided for the treatment of gastric ulcer-prone patients in view of the recent evidence.sup.1 that hyperchlorohydria may in fact not be the primary causative agent for gastric ulcer. It now appears that reflux of duodenal contents, especially bile, is an important etiologic factor in the formation of gastric ulcer. It has been found that the stomach of a patient with gastric ulcer contains bile more frequently and at higher concentrations than is found in the stomach of a normal subject. In an effort to explain this, studies have shown that in normal subjects, the pylorus functions as a sphincter which has the capacity to prevent retrograde movement of duodenal contents into the stomach. The human pylorus is associated with a zone of high pressure that relaxes with antral peristalsis, contracts with endogenous or exogenous hormonal stimulation, and regulates the regurgitation of duodenal contents into the stomach. It appears, therefore, that the failure or malfunction of the pylorus to function in its capacity as an effective sphincter in certain persons gives rise to the elevated gastric bile acid levels in the stomach and renders such a person prone to gastric ulcer. FNT .sup.1. Fisher et al, The New England Journal of Medicine, 288, No. 6, pp. 273-276 (Feb. 8, 1973).
The present invention provides a method, entirely novel in its approach to treatment of the ulcer condition, which is directed toward counteracting the elevated levels of gastric bile acids caused by the aforementioned pyloric incompetence.